Considerable progress has been made to remedy transplant-related complications in patients receiving HLA-identical sibling donor marrow. While many stem cell grafts continue to be from this donor source, a greater proportion of transplants is being carried out with stem cells from alternative donors, including less well-matched family members and unrelated individuals. As a result, the spectrum of transplant-related complications has changed. These changes include an increased incidence and severity of graft-versus-host disease (GVHD), an increase in infectious complications, and an increased incidence of graft failure. The current grant proposes studies to define mechanisms responsible for these complications so that effective therapies can be developed. long- term follow-up-prevention and treatment of chronic GVHD, and infection prophylaxis will be addressed the first project. The second project will define the immunological function of novel MHC class 1 molecules (MICA and MICB) that are polymorphic and almost exclusively expressed in gut epithelium, and test the hypothesis that these molecules play important roles in the development of intestinal GVHD. The third project will address the problem of graft failure by testing the hypothesis that GVH reactions and cytomegalovirus infection compromise marrow function. A core on information management and statistical support complete the Program Project Grant.